Many alkylating mutagens and carcinogens are known to attack the 0-6 position of guanine. Data which have been obtained by administering carcinogens to whole animals indicate that the presence of this modification in the DNA of a particular organ correlates with tumor formation. Certain tissues, however, can remove 0-6 alkylguanine from their DNA and thereby protect themselves from alkylating carcinogens. Data from Lindahl's laboratory (0lsson and Lindahl, J. Biol. Chem. 255, 10569, 1980) have shown that repair of 0-6 methylguanine in bacterial DNA involves the transfer of the methyl group to an acceptor protein. Recent studies from our laboratory have shown that an acceptor protein is also present in rat liver cells. The studies proposed here would characterize this newly discovered acceptor factor and determine its role in protecting cells from carcinogens. The factor will be purified to determine whether there is a single specific protein involved in the transfer of a particular alkyl group. Repair of 0-6 methlyguanine will then be compared with repair of 0-6 ethylguanine to determine whether the same protein acceptor is involved in the repair of both lesions. Once purification has been achieved, the composition of the factor(s) will be elucidated and experiments will be performed to determine whether manipulation of the factor can enhance repair activity.